Transfusion-related acute lung injury (TRALI): a clinical review with emphasis on the critically ill

Abstract

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality world-wide. Although first described in 1983, it took two decades to develop consensus definitions, which remain controversial. The pathogenesis of TRALI is related to the infusion of donor antibodies that recognize leucocyte antigens in the transfused host or the infusion of lipids and other biological response modifiers that accumulate during the storage or processing of blood components. TRALI appears to be the result of at least two sequential events and treatment is supportive. This review demonstrates that critically ill patients are more susceptible to TRALI and require special attention by critical care specialists, haematologists and transfusion medicine experts. Further research is required into TRALI and its pathogenesis so that transfusions are safer and administered appropriately. Avoidance including male-only transfusion practises, the use of leucoreduced components, fresher blood/blood components and solvent detergent plasma are also discussed.

Figures

Figure 1. The pathophysiology of TRALI. Fig.1A Neutrophil-mediated TRALI

PMNs, which are sequestered by pro-inflammatory activation of the pulmonary microvascular endothelium, may be activated by the infusion of antibodies, which recognize the surface antigens expressed upon neutrophils, or biologically active lipids and/or sCD40L which activate distinct neutrophil receptors (Kelher, et al 2009, Khan, et al 2006). Antibodies, lipids, or sCD40L activate the microbicidal arsenal of the primed, sequestered neutrophils producing superoxide anion (O2-), which causes endothelial damage, capillary leak and ALI at the points of firm adhesion. Other causes of TRALI may present antigen antibody complexes on the surface of endothelium which are scavenged by the Fc receptors of neutrophils causing their activation and EC damage and ALI (Looney, et al 2006). Fig.1B TRALI in the absence of neutrophils. Lastly, permeability agents, such as vascular endothelial growth factor (VEGF) could activate pulmonary endothelium resulting in a decrease in the size of the endothelial cells rendering the pulmonary capillaries leaky resulting in non-cardiogenic pulmonary oedema and ALI (Boshkov 2000).

Figure 1. The pathophysiology of TRALI. Fig.1A Neutrophil-mediated TRALI

PMNs, which are sequestered by pro-inflammatory activation of the pulmonary microvascular endothelium, may be activated by the infusion of antibodies, which recognize the surface antigens expressed upon neutrophils, or biologically active lipids and/or sCD40L which activate distinct neutrophil receptors (Kelher, et al 2009, Khan, et al 2006). Antibodies, lipids, or sCD40L activate the microbicidal arsenal of the primed, sequestered neutrophils producing superoxide anion (O2-), which causes endothelial damage, capillary leak and ALI at the points of firm adhesion. Other causes of TRALI may present antigen antibody complexes on the surface of endothelium which are scavenged by the Fc receptors of neutrophils causing their activation and EC damage and ALI (Looney, et al 2006). Fig.1B TRALI in the absence of neutrophils. Lastly, permeability agents, such as vascular endothelial growth factor (VEGF) could activate pulmonary endothelium resulting in a decrease in the size of the endothelial cells rendering the pulmonary capillaries leaky resulting in non-cardiogenic pulmonary oedema and ALI (Boshkov 2000).

Figure 2. The Diagnosis and Management of TRALI

In a patient who developed ALI within 6 hours of transfusion other aetiologies of pulmonary oedema must be ruled out especially volume overload (TACO). If there are other risk factors for ALI present then a clinical determination of the role of the transfusion must be determined and if transfusion is thought to be etiologic then the observed ALI is TRALI. Antigen antibody testing is completed to aid in confirmation and if positive than the donor is excluded from future plasma donations. If negative, then the observed TRALI is likely due to other agents including lipids or sCD40L and testing may be done in Denver of Brisbane, currently for these agents. Management of TRALI involves supportive care and ventilation with low tidal volumes (Vt). Further transfusions should be minimized, a restrictive transfusion policy, and washing of cellular blood products to remove antibodies and other biologic response modifiers should be considered.